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1.
Cogn Neuropsychiatry ; : 1-14, 2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-39068667

RESUMO

INTRODUCTION: The study aims to use power spectrum changes in subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI), preclinical stages of Alzheimer's disease (AD), for future biomarker studies in early AD diagnosis. METHODS: We recruited 23 SCD and 32 aMCI subjects and conducted comparative analysis using relative power spectral density (PSD). Automated preprocessing and statistical analysis were performed using iSync Brain® (iMediSync Inc., Republic of Korea) (https://isyncbrain.com/). RESULTS: Theta band power in the temporal region was 14.826 ± 7.2394 for the SCD group and 20.003 ± 10.1768 for the aMCI group. In the parietal region, theta band power was 13.614 ± 7.5689 for SCD and 19.894 ± 11.1387 for aMCI. Beta1 band power in the frontal region was 6.639 ± 2.2904 for SCD and 5.465 ± 1.8907 for aMCI, and in the temporal region it was 7.359 ± 2.5619 for SCD and 5.921 ± 2.1605 for aMCI. CONCLUSION: PSD analysis of resting-state EEG predicted SCD, a preclinical stage of AD. This cross-sectional study observed electrical-physiological characteristics of preclinical AD; however, follow-up studies are needed to evaluate predictive value for future cognitive decline.

2.
J Clin Med ; 13(14)2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-39064073

RESUMO

Background/Objectives: This study aimed to evaluate bone mineral density (BMD) discordance and its implications in veterans with unilateral lower-limb amputation, emphasizing the need for comprehensive hip assessments. Methods: Data were collected from 84 male veterans, and BMD was measured using dual-energy X-ray absorptiometry (DXA) at the lumbar spine, intact hip, and amputated hip. Results: The T-scores for the lumbar spine, intact hip, and amputated hip were -0.27 ± 1.69, -0.25 ± 1.20, and -1.07 ± 1.33, respectively. Osteoporosis and osteopenia were present in 19% and 34.6% of patients, respectively. Osteopenia and osteoporosis were most prevalent in the hips on the amputated side (32.1% and 13.1%, respectively), followed by the lumbar spines (22.6% and 8.3%) and the hips on the intact side (17.9% and 2.4%). BMD discordance between the lumbar spine and hip was found in 47.6% of participants, while discordance between both hips was observed in 39.3%. Transfemoral amputees had significantly lower BMD at the amputated hip compared to transtibial amputees (-2.38 ± 1.72 vs. -0.87 ± 1.16, p < 0.001). Conclusions: Veterans with unilateral lower-limb amputation exhibit a high prevalence of osteoporosis and significant BMD discordance, particularly between both hips. These findings underscore the necessity for bilateral hip assessments to ensure the accurate diagnosis and effective management of osteoporosis in this population.

3.
Cancer Res Treat ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38965924

RESUMO

Purpose: Proximal gastrectomy is an alternative to total gastrectomy (TG) for early gastric cancer (EGC) treatment in the upper stomach. However, its benefits in terms of perioperative and long-term outcomes remain controversial. The aim of this study was to compare the perioperative, body compositional, nutritional, and survival outcomes of patients undergoing proximal gastrectomy with double-tract reconstruction (PG-DTR) and TG for pathological stage I gastric cancer in upper stomach. Materials and Methods: The study included 506 patients who underwent gastrectomy for pathological stage I gastric cancer in the upper stomach between 2015 and 2019. Clinicopathological, perioperative, body compositional, nutritional, and survival outcomes were compared between the PG-DTR and TG groups. Results: The PG-DTR and TG groups included 197 (38.9%) and 309 (61.1%) patients, respectively. The PG-DTR group had a lower rate of early complications (p=0.041), lower diagnosis rate of anemia and vitamin B12 deficiency (all p<0.001), and lower replacement rate of iron and vitamin B12 compared to TG group (all p<0.001). The PG-DTR group showed reduced incidence of sarcopenia at 6-months postoperatively, preserved higher amount of visceral fat after surgery (p=0.032 and p=0.040, respectively), and showed a higher hemoglobin level (p=0.007). Oncologic outcomes were comparable between the groups. Conclusion: The PG-DTR for EGC located in the upper stomach offered advantages of fewer complications, lower incidence of anemia and vitamin B12 deficiency, less decrease in visceral fat volume, and similar survival compared to TG. Consequently, PG-DTR may be considered a superior alternative treatment option to TG.

4.
Sensors (Basel) ; 24(13)2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-39000854

RESUMO

In the shipbuilding industry, welding automation using welding robots often relies on arc-sensing techniques due to spatial limitations. However, the reliability of the feedback current value, core sensing data, is reduced when welding target workpieces have significant curvature or gaps between curved workpieces due to the control of short-circuit transition, leading to seam tracking failure and subsequent damage to the workpieces. To address these problems, this study proposes a new algorithm, MBSC (median-based spatial clustering), based on the DBSCAN (density-based spatial clustering of applications with noise) clustering algorithm. By performing clustering based on the median value of data in each weaving area and considering the characteristics of the feedback current data, the proposed technique utilizes detected outliers to enhance seam tracking accuracy and responsiveness in unstructured and challenging welding environments. The effectiveness of the proposed technique was verified through actual welding experiments in a yard environment.

5.
Front Immunol ; 15: 1418249, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38994362

RESUMO

Introduction: Decreasing rates of blood donation and close margins between blood supply and demand pose challenges in healthcare. Genetically engineered pig red blood cells (pRBCs) have been explored as alternatives to human RBCs for transfusion, and triple-gene knockout (TKO) modification improves the compatibility of pRBCs with human blood in vitro. In this study, we assessed the efficacy and risks of transfusing wild-type (WT)- and TKO-pRBCs into nonhuman primates (NHPs). Methods: Blood from O-type WT and TKO pigs was processed to produce pRBCs for transfusion, which were transfused or not into NHPs (n=4 per group: WT, TKO, and control) after 25% total blood volume withdrawal: their biological responses were compared. Hematological, biochemical, and immunological parameters were measured before, immediately after, and at intervals following transfusion. Two months later, a second transfusion was performed in three NHPs of the transfusion group. Results: Transfusion of both WT- and TKO-pRBCs significantly improved RBC counts, hematocrit, and hemoglobin levels up to the first day post-transfusion, compared to the controls. The transfusion groups showed instant complement activation and rapid elicitation of anti-pig antibodies, as well as elevated liver enzyme and bilirubin levels post-transfusion. Despite the higher agglutination titers with WT-pRBCs in the pre-transfusion crossmatch, the differences between the WT and TKO groups were not remarkable except for less impairment of liver function in the TKO group. After the second transfusion, more pronounced adverse responses without any hematological gain were observed. Conclusions: WT- and TKO-pRBC transfusions effectively increased hematologic parameters on the first day, with rapid clearance from circulation thereafter. However, pRBC transfusion triggers strong antibody responses, limiting the benefits of the pRBC transfusion and increasing the risk of adverse reactions.


Assuntos
Transfusão de Eritrócitos , Eritrócitos , Técnicas de Inativação de Genes , Animais , Transfusão de Eritrócitos/efeitos adversos , Transfusão de Eritrócitos/métodos , Suínos , Eritrócitos/imunologia , Eritrócitos/metabolismo , Animais Geneticamente Modificados , Hemoglobinas/metabolismo , Galactosiltransferases/genética , Galactosiltransferases/deficiência , Hematócrito , Feminino , Masculino , Primatas
6.
Traffic Inj Prev ; : 1-7, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38996007

RESUMO

OBJECTIVE: Driving under the influence (DUI) of alcohol is a major risk factor for fatal road traffic injuries (RTIs) worldwide. This study aimed to investigate the relationship between the implementation of new acts on DUI of alcohol and the clinical outcomes of patients with severe RTIs in Korea. METHODS: This is a community-based cross-sectional study using a nationwide severe trauma registry in Korea. In 2018, 2 acts with the Yoon Chang-Ho Act (Yoon's Act) were passed to strengthen the punishment for drunk driving fatal RTIs (first Yoon's act) and lower the blood alcohol concentration limit to restrict driver's licenses (second Yoon's act). The first Yoon's act was implemented on December 18, 2018, and the second Yoon's act was implemented on June 25, 2019. The study periods were categorized as pre-Act-1, pre-Act-2, Act-1, and Act-2 according to the application of Yoon's Act, and the study outcome was in-hospital mortality. Multivariable logistic regression analysis was conducted to estimate the relationship of the new acts and in-hospital mortality. RESULTS: Among a total of 20,376 patients with severe RTIs and 7,928 patients (drivers) with RTIs (hereafter drivers), the in-hospital mortality rates were 20.8% and 17.0%, and alcohol-related RTIs accounted for 9.7% and 8.1%, respectively. Severe RTIs tended to increase with each period (25.5 cases/day, 24.5 cases/day, 26.8 cases/day, and 30.4 cases/day, P for trend <.01). In-hospital mortality significantly decreased during the Act-2 period compared to the pre-Act-2 period for all patients with severe RTIs (adjusted odds ratio = 0.54, 95% confidence interval 0.43-0.67) and drivers with RTIs (adjusted odds ratio = 0.50, 95% confidence interval 0.34-0.73). CONCLUSIONS: Implementation of the new acts on DUI of alcohol was associated with lower odds for in-hospital mortality for patients with severe RTIs. Further studies are needed to evaluate the long-term impact of the new acts on reducing alcohol-related RTIs.

7.
Sci Rep ; 14(1): 15923, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987613

RESUMO

Tuberculosis is a highly contagious disease caused by Mycobacterium tuberculosis (Mtb), which is one of the prominent reasons for the death of millions worldwide. The bacterium has a substantially higher mortality rate than other bacterial diseases, and the rapid rise of drug-resistant strains only makes the situation more concerning. Currently, the only licensed vaccine BCG (Bacillus Calmette-Guérin) is ineffective in preventing adult pulmonary tuberculosis prophylaxis and latent tuberculosis re-activation. Therefore, there is a pressing need to find novel and safe vaccines that provide robust immune defense and have various applications. Vaccines that combine epitopes from multiple candidate proteins have been shown to boost immunity against Mtb infection. This study applies an immunoinformatic strategy to generate an adequate multi-epitope immunization against Mtb employing five antigenic proteins. Potential B-cell, cytotoxic T lymphocyte, and helper T lymphocyte epitopes were speculated from the intended proteins and coupled with 50 s ribosomal L7/L12 adjuvant, and the vaccine was constructed. The vaccine's physicochemical profile demonstrates antigenic, soluble, and non-allergic. In the meantime, docking, molecular dynamics simulations, and essential dynamics analysis revealed that the multi-epitope vaccine structure interacted strongly with Toll-like receptors (TLR2 and TLR3). MM-PBSA analysis was performed to ascertain the system's intermolecular binding free energies accurately. The immune simulation was applied to the vaccine to forecast its immunogenic profile. Finally, in silico cloning was used to validate the vaccine's efficacy. The immunoinformatics analysis suggests the multi-epitope vaccine could induce specific immune responses, making it a potential candidate against Mtb. However, validation through the in-vivo study of the developed vaccine is essential to assess its efficacy and immunogenicity profile, which will assure active protection against Mtb.


Assuntos
Biologia Computacional , Epitopos de Linfócito T , Mycobacterium tuberculosis , Vacinas contra a Tuberculose , Vacinas de Subunidades Antigênicas , Mycobacterium tuberculosis/imunologia , Vacinas de Subunidades Antigênicas/imunologia , Vacinas contra a Tuberculose/imunologia , Biologia Computacional/métodos , Humanos , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito B/imunologia , Simulação de Dinâmica Molecular , Simulação de Acoplamento Molecular , Antígenos de Bactérias/imunologia , Tuberculose/prevenção & controle , Tuberculose/imunologia , Receptor 2 Toll-Like/imunologia , Imunoinformática
9.
Foods ; 13(13)2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38998472

RESUMO

Chili peppers (Capsicum annuum L.) are economically valuable crops belonging to the Solanaceae family and are popular worldwide because of their unique spiciness and flavor. In this study, differences in the metabolomes of landrace (Subicho) and disease-resistant pepper cultivars (Bulkala and Kaltanbaksa) widely grown in Korea are investigated using a 1H NMR-based metabolomics approach. Specific metabolites were abundant in the pericarp (GABA, fructose, and glutamine) and placenta (glucose, asparagine, arginine, and capsaicin), highlighting the distinct physiological and functional roles of these components. Both the pericarp and placenta of disease-resistant pepper cultivars contained higher levels of sucrose and hexoses and lower levels of alanine, proline, and threonine than the traditional landrace cultivar. These metabolic differences are linked to enhanced stress tolerance and the activation of defense pathways, imbuing these cultivars with improved resistance characteristics. The present study provides fundamental insights into the metabolic basis of disease resistance in chili peppers, emphasizing the importance of multi-resistant varieties to ensure sustainable agriculture and food security. These resistant varieties ensure a stable supply of high-quality peppers, contributing to safer and more sustainable food production systems.

10.
Anat Cell Biol ; 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39048513

RESUMO

Vitamin C is a well-known antioxidant with antiviral, anticancer, and anti-inflammatory properties based on its antioxidative function. Aptamin C, a complex of vitamin C with its specific aptamer, has been reported to maintain or even enhance the efficacy of vitamin C while increasing its stability. To investigate in vivo distribution of Aptamin C, Gulo knockout mice, which, like humans, cannot biosynthesize vitamin C, were administered Aptamin C orally for 2 and 4 weeks. The results showed higher vitamin C accumulation in all tissues when administered Aptamin C, especially in the spleen. Next, the activity of natural killer (NK) cells were conducted. CD69, a marker known for activating for NK cells, which had decreased due to vitamin C deficiency, did not recover with vitamin C treatment but showed an increasing with Aptamin C. Furthermore, the expression of CD107a, a cell surface marker that increases during the killing process of target cells, also did not recover with vitamin C but increased with Aptamin C. Based on these results, when cultured with tumor cells to measure the extent of tumor cell death, an increase in tumor cell death was observed. To investigate the signaling mechanisms and related molecules involved in the proliferation and activation of NK cells by Aptamin C showed that Aptamin C treatment led to an increase in intracellular STAT3 activation. In conclusion, Aptamin C has a higher capability to activate NK cells and induce tumor cell death compared to vitamin C and it is mediated through the activation of STAT3.

11.
Epidemiol Health ; : e2024066, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39054626

RESUMO

Objectives: This study investigated the associations between several obesity-related anthropometric indices and mortality in middle-aged and elderly populations to compare the indices' predictive ability with that of the body mass index (BMI). Methods: We analyzed data on 12 indices calculated from 19,805 community-based cohort participants (average age, 63.27 years; median follow-up, 13.49 years). Each index was calculated using directly measured values of height, weight, waist circumference (WC), and hip circumference (HC). We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for each index using Cox regression and evaluated mortality prediction with the Harrell c-index. Results: Adding anthropometric indices to the basic mortality model (c-index 0.7723; 95% CI, 0.7647-0.7799) significantly increased the predictive power of BMI (c-index 0.7735; 95% CI, 0.7659-0.7811), a body shape index (ABSI, c-index 0.7735; 95% CI, 0.7659-0.7810), weight-adjusted waist index (WWI, c-index 0.7731; 95% CI, 0.7656-0.7807), and waist to hip index (WHI, c-index 0.7733; 95% CI, 0.7657-0.7809). The differences between the BMI model and the other 3 models were not statistically significant. Conclusion: In predicting all-cause mortality, the ABSI, WWI, and WHI models based on WC or HC had stronger predictive power than conventional risk factors but were not significantly different from the BMI model.

12.
Chem Biol Interact ; 399: 111134, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38969276

RESUMO

Polyhexamethyleneguanidine phosphate (PHMG-P) is a biocide of guanidine family that can cause a fatal lung damage if exposed directly to the lungs. No reports exist regarding the toxicity of PHMG-P in neonatal animals. Therefore, this study aimed to determine PHMG-P toxicity in neonatal and 8-week-old mice after they were intranasally instilled with 1.5 mg/kg, 3 mg/kg, and 4.5 mg/kg PHMG-P. PHMG-P lung exposure resulted in more severe pulmonary toxicity in adult mice than in newborn mice. In the high-dose group of newborn mice, a minimal degree of inflammatory cell infiltration and fibrosis in the lung were detected, whereas more severe pathological lesions including granulomatous inflammation, fibrosis, and degeneration of the bronchiolar epithelium were observed in adult mice. At day 4, C-C motif chemokine ligand 2 (CCL2), a potent chemokine for monocytes, was upregulated but recovered to normal levels at day 15 in newborn mice. However, increased CCL2 and IL-6 levels were sustained at day 15 in adult mice. When comparing the differentially expressed genes of newborn and adult mice through RNA-seq analysis, there were expression changes in several genes associated with inflammation in neonates that were similar or different from those in adults. Although no significant lung damage occurred in newborns, growth inhibition was observed which was not reversed until the end of the experiment. Further research is needed to determine how growth inhibition from neonatal exposure to PHMG-P affects adolescent and young adult health.

13.
Clin Orthop Surg ; 16(3): 413-421, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38827750

RESUMO

Background: Posterior femoral condylar osteophytes were frequently observed in patients with the ultra-congruent (UC) deep-dish design prosthesis. Therefore, the purpose of the present study was to verify the clinical relevance of osteophyte formation in the UC design. Methods: From March 2014 to February 2018, a comparative study was conducted on 96 knees using the UC design. They were divided into 2 groups (group 1: osteophyte +, group 2: osteophyte -). Intraoperative findings, indirect femoral rollback assessment using 30° flexion and active full flexion lateral radiographs, serial change of the osteophyte, and outcomes were compared. Results: The mean follow-up period was 49.35 ± 3.47 months in group 1 and 47.52 ± 3.37 months in group 2. Posterior component coverage was significantly different between the groups: group 1 exhibited more underhang and group 2 exhibited more overhang (p = 0.022). On the indirect assessment of the femoral rollback, there was a statistically significant difference in deep flexion and change in distance (p < 0.001 and p < 0.001, respectively). There was no statistical difference between the 2 groups in the American Knee Society knee and function score, and group 2 showed significant improvement in pain compared to group 1 in Western Ontario and McMaster University Arthritis Index pain score (p = 0.029). Conclusions: Posterior condylar osteophyte formation was related to posterior impingement. It was more frequently observed in the underhang of the femoral component and insufficient femoral rollback. In addition, it changed with time and caused negative effects, including a gradual decrease in flexion and more pain.


Assuntos
Artroplastia do Joelho , Osteófito , Humanos , Osteófito/diagnóstico por imagem , Feminino , Masculino , Idoso , Artroplastia do Joelho/métodos , Pessoa de Meia-Idade , Radiografia , Prótese do Joelho , Desenho de Prótese , Amplitude de Movimento Articular , Estudos Retrospectivos , Osteoartrite do Joelho/cirurgia , Osteoartrite do Joelho/diagnóstico por imagem , Relevância Clínica
14.
Injury ; : 111630, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38839516

RESUMO

OBJECTIVES: The aim of this study was to investigate the association between patient age and guideline adherence for prehospital care in emergency medical services (EMS) for moderate to severe trauma. METHODS: This was a retrospective observational study that used a nationwide EMS-based trauma database from 2016 to 2019. Adult trauma patients whose injury severity score was greater than or equal to nine were screened, and those with cardiac arrest or without outcome data were excluded. The enrolled patients were categorized into four groups according to patient age: young (<45 years), middle-aged (45-64 years), old (65-84 years), and very old (>84 years). The primary outcome was guideline adherence, which was defined as following all prehospital care components: airway management for level of consciousness below verbal response, oxygen supply for pulse oximetry under 94 %, intravenous fluid administration for systolic blood pressure under 90 mmHg, scene resuscitation time within 10 min, and transport to the trauma center or level 1 emergency department. Multivariable logistic regression was conducted to calculate the adjusted odds ratios (aORs) and 95 % confidence intervals (95 % CIs). RESULTS: Among the 430,365 EMS-treated trauma patients, 38,580 patients were analyzed-9,573 (24.8 %) in the young group, 15,296 (39.7 %) in the middle-aged group, 9,562 (24.8 %) in the old group, and 4,149 (10.8 %) in the very old group. The main analysis revealed a lower probability of guideline adherence in the old group (aOR 95 % CI = 0.84 (0.76-0.94)) and very old group (aOR 95 % CI = 0.68 (0.58-0.81)) than in the young group. CONCLUSION: We found disparities in guideline adherence for prehospital care according to patient age at the time of EMS assessment of moderate to severe trauma. Considering this disparity, the prehospital trauma triage and management for older patients needs to be improved and educated to EMS providers.

15.
Sci Adv ; 10(26): eadn6217, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38924417

RESUMO

Although advanced robots can adeptly mimic human movement and aesthetics, they are still unable to adapt or evolve in response to external experiences. To address this limitation, we propose an innovative approach that uses parallel-processable retention-engineered synaptic devices in the control system. This approach aims to simulate a human-like learning system without necessitating complex computational systems. The retention properties of the synaptic devices were modulated by adjusting the amount of Ag/AgCl ink sprayed. This changed the voltage drop across the interface between the gate electrode and the electrolyte. Furthermore, the unrestricted movement of ions in the electrolyte enhanced the signal multiplexing capability of the ion gel, enabling device-level parallel processing. By integrating the unique characteristics of the synaptic devices with actuators, we successfully emulated a human-like workout process that includes feedback between acute and chronic responses. The proposed control system offers an innovative approach to reducing system complexity and achieving a human-like learning system in the field of biomimicry.


Assuntos
Robótica , Humanos , Robótica/métodos , Sinapses/fisiologia , Biomimética/métodos
16.
Nutrients ; 16(12)2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38931199

RESUMO

Saikosaponin D (SSD), derived from Bupleurum falcatum L., has various pharmacological properties, including immunoregulatory, anti-inflammatory, and anti-allergic effects. Several studies have investigated the anti-tumor effects of SSD on cancer in multiple organs. However, its role in colorectal cancer (CRC) remains unclear. Therefore, this study aimed to elucidate the suppressive effects of SSD on CRC cell survival and metastasis. SSD reduced the survival and colony formation ability of CRC cells. SSD-induced autophagy and apoptosis in CRC cells were measured using flow cytometry. SSD treatment increased LC3B and p62 autophagic factor levels in CRC cells. Moreover, SSD-induced apoptosis occurred through the cleavage of caspase-9, caspase-3, and PARP, along with the downregulation of the Bcl-2 family. In the in vivo experiment, a reduction in the number of metastatic tumor nodules in the lungs was observed after the oral administration of SSD. Based on these results, SSD inhibits the metastasis of CRC cells to the lungs by inducing autophagy and apoptosis. In conclusion, SSD suppressed the proliferation and metastasis of CRC cells, suggesting its potential as a novel substance for the metastatic CRC treatment.


Assuntos
Apoptose , Autofagia , Neoplasias Colorretais , Neoplasias Pulmonares , Ácido Oleanólico , Saponinas , Saponinas/farmacologia , Ácido Oleanólico/farmacologia , Ácido Oleanólico/análogos & derivados , Autofagia/efeitos dos fármacos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/tratamento farmacológico , Apoptose/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Antineoplásicos Fitogênicos/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , Sobrevivência Celular/efeitos dos fármacos , Camundongos Nus
17.
Int J Stroke ; : 17474930241265652, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38907672

RESUMO

BACKGROUND: Multiple attempts of thrombectomy have been linked to a higher risk of intracerebral hemorrhage and worsened functional outcomes, potentially influenced by blood pressure (BP) management strategies. Nonetheless, the impact of intensive BP management following successful recanalization through multiple attempts remains uncertain. AIMS: This study aimed to investigate whether conventional and intensive BP management differentially affect outcomes according to multiple-attempt recanalization (MAR) and first-attempt recanalization (FAR) groups. METHODS: In this secondary analysis of the OPTIMAL-BP trial, which was a comparison of intensive (systolic BP target <140 mm Hg) and conventional (systolic BP target 140-180 mm Hg) BP managements during the 24 hours after successful recanalization, we included intention-to-treat population of the trial. Patients were divided into the MAR and the FAR groups. We examined a potential interaction between the number of thrombectomy attempts (MAR and FAR groups) and the effect of BP managements on clinical and safety outcomes. The primary outcome was functional independence at 3 months. Safety outcomes were symptomatic intracerebral hemorrhage within 36 hours and mortality within 3 months. RESULTS: Of the 305 patients (median 75 years), 102 (33.4%) were in the MAR group and 203 (66.6%) were in the FAR group. The intensive BP management was significantly associated with a lower rate of functional independence in the MAR group (intensive, 32.7% vs. conventional, 54.9%, adjusted OR 0.33, 95% CI 0.12-0.90, p = 0.03). In the FAR group, the proportion of patients with functional independence was not significantly different between the BP managements (intensive, 42.5% vs. conventional, 54.2%, adjusted OR 0.73, 95% CI 0.38-1.40). Incidences of symptomatic intracerebral hemorrhage and mortality rates were not significantly different according to the BP managements in both MAR and FAR groups. CONCLUSIONS: Among stroke patients who received multiple attempts of thrombectomy, intensive BP management for 24 hours resulted in a reduced chance of functional independence at 3 months and did not reduce symptomatic intracerebral hemorrhage following successful reperfusion.

18.
Prehosp Emerg Care ; : 1-7, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38830202

RESUMO

OBJECTIVES: The effect of the case volume of emergency medical services (EMS) on the clinical outcomes of trauma is uncertain. The purpose of this study was to evaluate the association between the case volume of an ambulance station and clinical outcomes in moderate to severe trauma patients. METHODS: Adult trauma patients with injury severity scores greater than 8 who were transported by the EMS between 2018 and 2019 were analyzed. The main exposure was the annual case volume of moderate to severe trauma at the ambulance station where the patient-transporting ambulance was based: low-volume (less than 60 cases), intermediate-volume (between 60 and 89 cases), and high-volume (equal or greater than 90 cases). The primary outcome was in-hospital mortality. Multilevel multivariable logistic regression analysis was conducted to calculate adjusted odds ratios (AORs) and 95% confidence intervals (CIs), with the high-volume group used as the reference. RESULTS: In total, 21,498 trauma patients were analyzed. The high-volume group exhibited lower in-hospital mortality, 447 (9.0%), compared to 867 (14.1%) in the intermediate-volume group and 1,458 (14.1%) in the low-volume group. There were a significantly higher odds of in-hospital mortality: the low-volume group (AOR 95% CI: 1.20 (0.95-1.51)) and intermediate-volume group (AOR 95% CI: 1.29 (1.02-1.64)) when compared to the high-volume group. CONCLUSIONS: The case volume at an ambulance station is associated with in-hospital mortality in patients with moderate to severe trauma. These results should be considered when constructing an EMS system and education program for prehospital trauma care.

19.
Artigo em Inglês | MEDLINE | ID: mdl-38866622

RESUMO

BACKGROUND AND AIMS: Vitamin D is known to influence the risk of cardiovascular disease, which is a recognized risk factor for sudden cardiac arrest (SCA). However, the relationship between vitamin D and SCA is not well understood. Therefore, this study aims to investigate the association between vitamin D and SCA in out-of-hospital cardiac arrest (OHCA) patients compared to healthy controls. METHODS AND RESULTS: Using the Phase II Cardiac Arrest Pursuit Trial with Unique Registration and Epidemiologic Surveillance (CAPTURES II) registry, a 1:1 propensity score-matched case-control study was conducted between 2017 and 2020. Serum 25-hydroxyvitamin D (vitamin D) levels in patients with OHCA (454 cases) and healthy controls (454 cases) were compared after matching for age, sex, cardiovascular risk factors, and lifestyle behaviors. The mean vitamin D levels were 14.5 ± 7.6 and 21.3 ± 8.3 ng/mL among SCA cases and controls, respectively. Logistic regression analysis was used adjusting for cardiovascular risk factors, lifestyle behaviors, corrected serum calcium levels, and estimated glomerular filtration rate (eGRF). The adjusted odds ratio (aOR) for vitamin D was 0.89 (95% confidence interval [CI] 0.87-0.91). The dose-response relationship demonstrated that vitamin D deficiency was associated with SCA incidence (severe deficiency, aOR 10.87, 95% CI 4.82-24.54; moderate deficiency, aOR 2.24, 95% CI 1.20-4.20). CONCLUSION: Vitamin D deficiency was independently and strongly associated with an increased risk of SCA, irrespective of cardiovascular and lifestyle factors, corrected calcium levels, and eGFR.

20.
Mol Cells ; 47(7): 100074, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38901530

RESUMO

Although binge alcohol-induced gut leakage has been studied extensively in the context of reactive oxygen species-mediated signaling, it was recently revealed that post-transcriptional regulation plays an essential role as well. Ethanol (EtOH)-inducible cytochrome P450-2E1 (CYP2E1), a key enzyme in EtOH metabolism, promotes alcohol-induced hepatic steatosis and inflammatory liver disease, at least in part by mediating changes in intestinal permeability. For instance, gut leakage and elevated intestinal permeability to endotoxins have been shown to be regulated by enhancing CYP2E1 mRNA and CYP2E1 protein levels. Although it is understood that EtOH promotes CYP2E1 induction and activation, the mechanisms that regulate CYP2E1 expression in the context of intestinal damage remain poorly defined. Specific miRNAs, including miR-132, miR-212, miR-378, and miR-552, have been shown to repress the expression of CYP2E1, suggesting that these miRNAs contribute to EtOH-induced intestinal injury. Here, we have shown that CYP2E1 expression is regulated post-transcriptionally through miRNA-mediated degradation, as follows: (1) the RNA-binding protein AU-binding factor 1 (AUF1) binds mature miRNAs, including CYP2E1-targeting miRNAs, and this binding modulates the degradation of corresponding target mRNAs upon EtOH treatment; (2) the serine/threonine kinase mammalian Ste20-like kinase 1 (MST1) mediates oxidative stress-induced phosphorylation of AUF1. Those findings suggest that reactive oxygen species-mediated signaling modulates AUF1/miRNA interaction through MST1-mediated phosphorylation. Thus, our study demonstrates the critical functions of AUF1 phosphorylation by MST1 in the decay of miRNAs targeting CYP2E1, the stabilization of CYP2E1 mRNA in the presence of EtOH, and the relationship of this pathway to subsequent intestinal injury.


Assuntos
Citocromo P-450 CYP2E1 , Etanol , MicroRNAs , Citocromo P-450 CYP2E1/metabolismo , Citocromo P-450 CYP2E1/genética , MicroRNAs/metabolismo , MicroRNAs/genética , Etanol/toxicidade , Etanol/efeitos adversos , Humanos , Animais , Ribonucleoproteína Nuclear Heterogênea D0/metabolismo , Intestinos/patologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia
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